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New Approaches for Tailoring the Use of Radiotherapy in Early-Stage Breast Cancer

  • Local-Regional Evaluation and Therapy (EP Mamounas, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The majority of women diagnosed with early-stage breast cancer will undergo radiotherapy. Clinical decisions regarding the delivery of radiotherapy are typically based on clinical and pathologic factors. In contrast, systemic therapy clinical decisions incorporate specific breast cancer biology. This review will focus on how breast cancer biology may help tailor radiotherapy for early-stage patients.

Recent Findings

Radiotherapy for early-stage breast cancer is typically delivered for breast conservation. Regional nodal radiotherapy use in early-stage disease is expected to expand in the wake of recent clinical trial publications demonstrating improved disease-free survival in those with one to three axillary nodal metastases. There is a growing body of data demonstrating that intrinsic breast cancer subtypes and luminal multigene assays developed for systemic therapy are also associated with local regional recurrence.

Summary

Including tumor biology in addition to standard clinical and pathological factors may lead to a more tailored use of radiotherapy in early-stage breast cancer.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Siegel R, Miller K, Jemal A. Cancer statistics 2016. CA Cancer J Clin. 2016;66:7–30.

    Article  PubMed  Google Scholar 

  2. Sareigo J. Regional variation in breast cancer treatment throughout the United States. Am J Surg. 2008;196:572–4.

    Article  Google Scholar 

  3. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual, 7th ed. France: Springer; 2010.

  4. Agarwal S, Pappas L, Neumayer L, et al. Effect of breast conservation therapy vs mastectomy on disease-specific survival for early-stage breast cancer. JAMA Surg. 2014;149(3):267–74.

    Article  PubMed  Google Scholar 

  5. EBCTCG (Early Breast Cancer Trialists’ Collaborative Group). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomized trials. Lancet. 2014;383:2127–35.

    Article  Google Scholar 

  6. Poortmans PM, Collette S, Kirkove C, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;374(4):317–27.

    Article  Google Scholar 

  7. Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373(4):307–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sorlie T, Perou C, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. PNAS. 2001;98(19):10869–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Peppercorn J, Perou CM, Carey LA. Molecular subtypes in breast cancer evaluation and management: divide and conquer. Cancer Investig. 2008;26:1–10.

    Article  CAS  Google Scholar 

  10. Prat A, Pineda E, Adamo B, et al. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast. 2015;24:S26–35.

    Article  PubMed  Google Scholar 

  11. Sineshaw HM, Gaudet M, Ward EM, et al. Association of race/ethnicity, socioeconomic status, and breast cancer subtypes in the National Cancer Data Base (2010–2011). Breast Cancer Res Treat. 2014;145:753–63.

    Article  PubMed  Google Scholar 

  12. Harris L, Ismaila N, McShane L, et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34:1134–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tuttle T, Jarosek S, Habermann E, et al. Omission of radiation therapy after breast-conserving surgery in the United States. Cancer. 2012;118:2004–13.

    Article  PubMed  Google Scholar 

  14. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet. 2005;366(9503):2087–106.

    Article  CAS  PubMed  Google Scholar 

  15. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomized trials. Lancet. 2011;378:1707–16.

    Article  Google Scholar 

  16. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomized trials. Lancet. 2011;378:771–84.

    Article  Google Scholar 

  17. Pegram MD, Pauletti G, Slamon DJ, et al. HER-2/neu as a predictive marker of response to breast cancer therapy. Breast Cancer Res Treat. 1998;52(1–3):65–77.

    Article  CAS  PubMed  Google Scholar 

  18. Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31:2382–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fisher B, Bryant J, Dignam JJ, et al. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol. 2002;20:4141–9.

    Article  CAS  PubMed  Google Scholar 

  20. Fyles AW, McCready DR, Manchul LA, et al. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med. 2004;351:963–70.

    Article  CAS  PubMed  Google Scholar 

  21. Arvold N, Taghian A, Niemierko A, et al. Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol. 2010;29:3885–91.

    Article  Google Scholar 

  22. Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 2010;28:1684–91.

    Article  PubMed  Google Scholar 

  23. • Liu F, Shi W, Done S, et al. Identification of a low-risk luminal a breast cancer cohort that may not benefit from breast radiotherapy. J Clin Oncol. 2015;33:2035–40. This manuscript demonstrated the importance of intrinsic subtype reconstructed by IHC and its relation to LRR in clinical trial samples from a population of all hormone-sensitive, node-negative breast cancer that was randomized to receive radiotherapy or observation after lumpectomy. By combining luminal A intrinsic subtype and clinical pathologic factors, they identified a cohort that had very low LRR after lumpectomy without radiotherapy.

    Article  PubMed  Google Scholar 

  24. Cardoso F, van’t Veer LJ, Bogaerts J, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375:717–29.

    Article  CAS  PubMed  Google Scholar 

  25. Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of loco regional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol. 2010;28:1677–83.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Solin LJ, Gray R, Goldstein LJ, et al. Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early stage breast carcinoma: results from the Eastern Cooperative Oncology Group E2197 study. Breast Cancer Res Treat. 2012;134:683–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fitzal F, Filipits M, Fesl C, et al. Predicting local recurrence using PAM50 in postmenopausal endocrine responsive breast cancer patients. J Clin Oncol. 2014;32:5s. (suppl; abstr 1008)

    Google Scholar 

  28. Fitzal F, Filipits M, Ruduas M, et al. The genomic expression test EndoPredict is a prognostic tool for identifying risk of local recurrence in postmenopausal endocrine receptor-positive, her2neu-negative breast cancer patients randomized within the prospective ABCSG 8 trial. Brit J Ca. 2015;112:1405–10.

    Article  CAS  Google Scholar 

  29. Drukker C, Elias S, Nijenhuis M, et al. Gene expression profiling to predict the risk of locoregional recurrence in breast cancer: a pooled analysis. Breast Cancer Res Treat. 2014;148:599–613.

    Article  CAS  PubMed  Google Scholar 

  30. Kyndi M, Sørensen FB, Knudsen H, et al. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2008;26:1419–26.

    Article  CAS  PubMed  Google Scholar 

  31. Kim M, Dawood S, Allen P, et al. Hormone receptor status influences the locoregional benefit of trastuzumab in patients with non-metastatic breast cancer. Cancer. 2012;118(20):4936–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang SL, Li YX, SONG YW, et al. Triple-negative or HER2-positive status predicts higher rates of locoregional recurrence in node-positive breast cancer patients after mastectomy. Int J Radiation Oncology Biol Phys. 2011;80(4):1095–101.

    Article  Google Scholar 

  33. Wu SG, He ZY, Li Q, et al. Predictive value of breast cancer molecular subtypes in Chinese patients with four or more positive nodes after postmastectomy radiotherapy. Breast. 2012;21:657–61.

    Article  PubMed  Google Scholar 

  34. • Tramm T, Mohammed H, Myhre S, et al. Development and validation of a gene profile predicting benefit of postmastectomy radiotherapy in patients with high-risk breast cancer: a study of gene expression in the DBCG 82bc cohort. Clin Cancer Res. 2014;20(20):5272–80. This manuscript reports on a seven-gene expression profile that was developed and validated from tissue samples collected on the DBCG82bc post-mastectomy clinical trials that are prognostic for LRR and predict radiotherapy benefit. Additional validation in other datasets is warranted for this assay that could potentially become an important clinical tool.

    Article  CAS  PubMed  Google Scholar 

  35. Tramm T, Kyndi M, Myhre S, et al. Relationship between the prognostic and predictive value of the intrinsic subtypes and a validated gene profile predictive of loco-regional control and benefit from post-mastectomy radiotherapy in patients with high-risk breast cancer. Acta Oncol. 2014;53:1337–46.

    Article  PubMed  Google Scholar 

  36. • Mamounas EP, Liu Q, Paik S, et al. 21-gene recurrence score and locoregional recurrence in node-positive/ER-positive breast cancer treated with chemo-endocrine therapy. JNCI J Natl Cancer Inst. 2017;109(4):djw259. This analysis demonstrated in tissue samples collected on the NSABP B-28 clinical trial that a biological factor like the Oncotype RS assay is prognostic for LRR in node-positive breast cancer treated with chemo-endocrine therapy and without regional nodal radiotherapy. Low LRR was reported in the low-risk or ≤18 RS groups, including those with four or more positive lymph nodes.

    Article  PubMed  Google Scholar 

  37. Woodward WA, Barlow WE, Jagsi R, et al. The 21-gene recurrence score and locoregional recurrence rates in patients with node-positive breast cancer treated on SWOG S8814. Int J Radiat Oncol Biol Phys. 96(2). S1-S268, e1-e717. 2016.

  38. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.

    Article  PubMed  Google Scholar 

  39. Mamounas EP, Anderson SJ, Dignam JJ, et al. Predictors of loco-regional recurrence following neoadjuvant chemotherapy: results from combined analysis of NSABP B-18 and B-27. J Clin Oncol. 2012;30(32):3960–6.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Stefanie Spielman Comprehensive Breast Center, The James, Ohio State University Comprehensive Cancer Center, 1145 Olentangy River Rd, Columbus, OH, 43212, USA

    Julia White

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  1. Julia White
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Correspondence to Julia White.

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Julia White declares that she has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Local-Regional Evaluation and Therapy

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White, J. New Approaches for Tailoring the Use of Radiotherapy in Early-Stage Breast Cancer. Curr Breast Cancer Rep 9, 129–136 (2017). https://doi.org/10.1007/s12609-017-0240-0

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  • DOI: https://doi.org/10.1007/s12609-017-0240-0

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